11-101452442-A-ATAAG

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_004621.6(TRPC6):c.*512_*513insCTTA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000888 in 158,822 control chromosomes in the GnomAD database, including 6 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00089 (6 hom., cov: 33)
  • Exomes 𝑓: 0.00092 (0 hom.)
• Consequence: TRPC6 NM_004621.6 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.991

Genes affected

TRPC6 (HGNC:12338): (transient receptor potential cation channel subfamily C member 6) The protein encoded by this gene forms a receptor-activated calcium channel in the cell membrane. The channel is activated by diacylglycerol and is thought to be under the control of a phosphatidylinositol second messenger system. Activation of this channel occurs independently of protein kinase C and is not triggered by low levels of intracellular calcium. Defects in this gene are a cause of focal segmental glomerulosclerosis 2 (FSGS2). [provided by RefSeq, Mar 2009]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 11-101452442-A-ATAAG is Benign according to our data. Variant chr11-101452442-A-ATAAG is described in ClinVar as [Likely_benign]. Clinvar id is 301889.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000886 (135/152286) while in subpopulation SAS AF= 0.0211 (102/4824). AF 95% confidence interval is 0.0178. There are 6 homozygotes in gnomad4. There are 90 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd at 118 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRPC6	NM_004621.6	c.*512_*513insCTTA		3_prime_UTR_variant	13/13	ENST00000344327.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRPC6	ENST00000344327.8	c.*512_*513insCTTA		3_prime_UTR_variant	13/13	1	NM_004621.6	P1

Frequencies

GnomAD3 genomes AF: 0.000775 AC: 118 AN: 152168 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.000169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000393

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.0213

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000918 AC: 6 AN: 6536 Hom.: 0 Cov.: 0 AF XY: 0.00173 AC XY: 6 AN XY: 3460

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00860

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.000886 AC: 135 AN: 152286 Hom.: 6 Cov.: 33 AF XY: 0.00121 AC XY: 90 AN XY: 74478

Gnomad4 AFR AF: 0.000168

Gnomad4 AMR AF: 0.000392

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000387

Gnomad4 SAS AF: 0.0211

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00851

Alfa AF: 0.000214 Hom.: 0

Bravo AF: 0.000215

Asia WGS AF: 0.0420 AC: 146 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Focal segmental glomerulosclerosis Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

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Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs557577176; hg19: chr11-101323173;